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An academic career in aging research is filled with the incredible highs of important discoveries that improve the lives of older adults and repeated lows when papers and grants are rejected or studies are negative. To normalize the experience of setbacks and failures in aging research, we invited three senior investigators to share their journeys of persistence and resilience as they have navigated their research careers. This career development symposium was presented at the 2021 Annual Scientific Meeting of the American Geriatrics Society, which was held virtually. We aimed to connect researchers in aging, especially trainees and junior investigators, through personal stories of persistence and shared strategies to build resilience and respond to setbacks with a growth mindset.

PURPOSE: To determine patient and disease characteristics associated with functional disability among adults with advanced non–small-cell lung cancer (NSCLC). METHODS: In a prospective cohort of participants newly diagnosed with advanced NSCLC and beginning systemic treatment, functional disability in usual activities, mobility, and self-care was measured using the EuroQol-5D-5L at baseline. Demographics, comorbidities, brain metastases, Eastern Cooperative Oncology Group performance status (ECOG PS), and psychologic variables (depression [Patient Health Questionnaire-9] and anxiety [Generalized Anxiety Disorder 7-item scale]) were captured. Patients were classified into two disability groups (none-slight or moderate-severe) on the basis of total functional status scores. Differences between disability groups were determined (chi-square and t tests). Associations between patient characteristics and baseline disability were assessed using logistic regression. RESULTS: Among 173 participants, mean age was 63.3 years, 56% were male, 83% had ECOG PS 0-1, and 41% had brain metastases. Baseline disability was present in 39% of participants, with patients having moderate to severe disability in usual activities (37.6%), mobility (26.6%), and self-care (5.2%). Depressive and/or anxiety symptoms ranged from none to severe (Patient Health Questionnaire 9-item scale M = 6.5, SD = 5.3). Depressive symptoms were the only characteristic associated with a higher odds of baseline disability (adjusted odds ratio [aOR]: 1.26; 95% CI, 1.15 to 1.38; P < .001). Participants with poorer ECOG PS (aOR: 4.64; 95% CI, 1.84 to 11.68; P = .001) and depressive symptoms (aOR: 1.15; 95% CI, 1.07 to 1.24; P < .001) had higher odds of moderate-severe mobility disability compared with the none-slight disability group. CONCLUSION: More than one third of all adults with advanced NSCLC have moderate-severe functional disability at baseline. Psychologic symptoms were significantly associated with moderate-severe baseline disability.

To improve the care of older adults with cancer, the traditional approach to clinical trial design needs to be reconsidered. Older adults are underrepresented in clinical trials with limited or no information on geriatric-specific factors, such as cognition or comorbidities. To address this knowledge gap and increase relevance of therapeutic clinical trial results to the real-life population, integration of aspects relevant to older adults is needed in oncology clinical trials. Geriatric assessment (GA) is a multidimensional tool comprising validated measures assessing specific health domains that are more frequently affected in older adults, including aspects related to physical function, comorbidity, medication use (polypharmacy), cognitive and psychological status, social support, and nutritional status. There are several mechanisms for incorporating either the full GA or specific GA measures into oncology therapeutic clinical trials to contribute to the overarching goal of the trial. Mechanisms include utilizing GA measures to better characterize the trial population, define trial eligibility, allocate treatment receipt within the context of the trial, develop predictive models for treatment outcomes, guide supportive care strategies, personalize care delivery, and assess longitudinal changes in GA domains. The objective of this manuscript is to review how GA measures can contribute to the overall goal of a clinical trial, to provide a framework to guide the selection and integration of GA measures into clinical trial design, and ultimately enable accrual of older adults to clinical trials by facilitating the design of trials tailored to older adults treated in clinical practice.

PURPOSE This Provisional Clinical Opinion update presents a clinically pragmatic approach to hepatitis B virus (HBV) screening and management. PROVISIONAL CLINICAL OPINION All patients anticipating systemic anticancer therapy should be tested for HBV by 3 tests—hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) total immunoglobulin (Ig) or IgG, and antibody to hepatitis B surface antigen—but anticancer therapy should not be delayed. Findings of chronic HBV (HBsAg-positive) or past HBV (HBsAg-negative and anti-HBc–positive) infection require HBV reactivation risk assessment. Patients with chronic HBV receiving any systemic anticancer therapy should receive antiviral prophylactic therapy through and for minimum 12 months following anticancer therapy. Hormonal therapy alone should not pose a substantial risk of HBV reactivation in patients with chronic HBV receiving hormonal therapy alone; these patients may follow noncancer HBV monitoring and treatment guidance. Coordination of care with a clinician experienced in HBV management is recommended for patients with chronic HBV to determine HBV monitoring and long-term antiviral therapy after completion of anticancer therapy. Patients with past HBV infection undergoing anticancer therapies associated with a high risk of HBV reactivation, such as anti-CD20 monoclonal antibodies or stem-cell transplantation, should receive antiviral prophylaxis during and for minimum 12 months after anticancer therapy completion, with individualized management thereafter. Careful monitoring may be an alternative if patients and providers can adhere to frequent, consistent follow-up so antiviral therapy may begin at the earliest sign of reactivation. Patients with past HBV undergoing other systemic anticancer therapies not clearly associated with a high risk of HBV reactivation should be monitored with HBsAg and alanine aminotransferase during cancer treatment; antiviral therapy should commence if HBV reactivation occurs. Additional information is available at www.asco.org/supportive-care-guidelines .

Immunotherapy with checkpoint inhibitors against programmed cell death receptor (PD-1) and programmed cell death ligand (PD-L1) has been implemented in the treatment pathway of patients with non-small cell lung cancer (NSCLC) from locally advanced disease to the metastatic setting. This approach has resulted in improved survival and a more favourable toxicity profile when compared with chemotherapy. Following the successful introduction of single-agent immunotherapy, current clinical trials are focusing on combination treatments with chemotherapy or radiotherapy or even other immunotherapeutic agents. However, most of the data available from these trials are derived from, and therefore might be more applicable to younger and fitter patients rather than older and often frail lung cancer real-world patients. This article provides a detailed review of these immunotherapy agents with a focus on the data available regarding older NSCLC patients and makes recommendations to fill evidence gaps in this patient population.

BACKGROUND: Shared decision making (SDM) is especially important for older adults with cancer given the risks of over- and undertreatment, uncertainty regarding benefits/harms worsened by research underrepresentation, and individual preferences. We aimed to adapt the Best Case/Worst Case (BC/WC) communication tool, which improves SDM in geriatric surgery, to geriatric oncology. METHODS: We conducted focus groups with 40 stakeholders (fourteen older adults with lung cancer, twelve caregivers, fourteen medical oncologists) to elicit perspectives on using the BC/WC tool for geriatric oncology and to identify components needing refinement. During each focus group, participants viewed a BC/WC demonstration video and answered questions modified from the Decision Aid Acceptability Scale. We analyzed transcripts using deductive and inductive thematic analyses. DISCUSSION: Participants believed that the BC/WC tool could help patients understand their cancer care choices, explore tradeoffs and picture potential outcomes, and deliberate about decisions based on their goals, preferences, and values. Oncologists also reported the tool could guide conversations to address points that may frequently be skipped (e.g., alternative options, treatment goals). Participant preferences varied widely regarding discussion of the worst-case scenario and desire for statistical information. CONCLUSION: The BC/WC tool is a promising strategy that may improve SDM in geriatric oncology and patient understanding of alternative options and treatment goals. Based on participant input, adaptations will include framing cancer care as a series of decisions, eliciting patient preferences and asking permission before offering the worst-case scenario, and selection of the two most relevant options to present if multiple exist.

BackgroundMaintenance of function during cancer treatment is important to older adults. Characteristics associated with pretreatment life-space mobility and changes during non-small cell lung cancer (NSCLC) treatment remain unknown.MethodsThis mixed methods cohort study recruited adults age ≥65 with advanced NSCLC starting palliative chemotherapy, immunotherapy, and/or targeted therapy from a Comprehensive Cancer Center, Veterans Affairs, and safety-net clinic. Patients completed geriatric assessments including Life-Space Assessment (LSA) pretreatment and at 1, 2, 4, and 6 months after treatment initiation. LSA scores range from 0 to 120 (greater mobility); LSA

ContextPatients with lung cancer who undergo chemotherapy (CTX) experience multiple symptoms. Evaluation of how these symptoms cluster together and how these symptom clusters change over time are salient questions in symptom clusters research.ObjectivesThe purposes of this analysis, in a sample of patients with lung cancer (n=145) who were receiving CTX, were to 1) evaluate for differences in the number and types of symptom clusters at three time points (i.e., before their next cycle of CTX, the week after CTX, and two weeks after CTX) using ratings of symptom occurrence and severity and 2) evaluate for changes in these symptom clusters over time.MethodsAt each assessment, a modified version of the Memorial Symptom Assessment Scale was used to assess the occurrence and severity of 38 symptoms. Exploratory factor analyses were used to extract the symptom clusters.ResultsAcross the two symptom dimensions (i.e., occurrence and severity) and the three assessments, six distinct symptom clusters were identified; however, only three of these clusters (i.e., lung cancer specific, psychological, nutritional) were relatively stable across both dimensions and across time. Two additional clusters varied by time but not by symptom dimension (i.e., epithelial/gastrointestinal and epithelial). A sickness behavior cluster was identified at each assessment with the exception of the week before CTX using only the severity dimension.ConclusionFindings provide insights into the most common symptom clusters in patients with lung cancer undergoing CTX. Most common symptoms within each cluster appear to be relatively stable across the two dimensions, as well as across time.

Background: Maintaining functional status is important to older adults with cancer, but data are limited on how systemic treatments affect functional status. We systematically reviewed changes in functional status during systemic cancer treatments and identified characteristics associated with functional decline and improvement. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Register of Controlled Trials for articles examining characteristics associated with functional changes in older adults during systemic cancer treatment published in English between database inception and January 11, 2019 (PROSPERO CRD42019123125). Findings were summarized with descriptive statistics. Study characteristics between older adult–specific and non–older adult–specific studies were compared using the Fisher exact test. Results: We screened 15,244 titles/abstracts and 519 full texts. The final analysis included 44 studies, which enrolled >8,400 patients; 39% of studies focused on older adults (1 study enrolled adults aged ≥60 years, 10 enrolled adults aged ≥65 years, and 6 enrolled adults aged ≥70 years). Almost all studies (98%) used patient-reported outcomes to measure functional status; only 20% used physical performance tests. Reporting of functional change was heterogeneous, with 48% reporting change scores. Older adult–specific studies were more likely to analyze functional change dichotomously (29% vs 4%; P=.008). Functional decline ranged widely, from 6% to 90%. The most common patient characteristics associated with functional decline were older age (n=7 studies), worse performance status (n=4), progressive disease status (n=4), pain (n=4), anemia (n=4), and worse nutritional status (n=4). Twelve studies examined functional improvement and identified 11 unique associated characteristics. Conclusions: Functional decline is increasingly recognized as an important outcome in older adults with cancer, but definitions and analyses are heterogeneous, leading to a wide range of prevalence. To identify patients at highest risk of functional decline during systemic cancer treatments, trials need to routinely analyze functional outcomes and measure characteristics associated with decline (eg, nutrition).

Background Prior comparisons of chemotherapy adverse events (AEs) by age and performance status (PS) are limited by the traditional maximum grade approach, which ignores low-grade AEs and longitudinal changes. Materials and Methods To compare fatigue and neuropathy longitudinally by age ( Results Older patients had on average a 0.17-point (95% confidence interval [CI], 0.00–0.34; p = .049) higher mean fatigue grade longitudinally compared with younger patients. PS 2 was associated with earlier development of grade ≥2 fatigue (hazard ratio [HR], 1.56; 95% CI, 1.07–2.27; p = .02). For neuropathy, older age was associated with earlier development of grade ≥2 neuropathy (HR, 1.41; 95% CI, 1.00–1.97; p = .049). Patients with PS 2 had a 1.30 point lower neuropathy AUC (95% CI, −2.36 to −0.25; p = .02) compared with PS 0–1. In contrast, maximum grade analyses only detected a higher percentage of older adults with grade ≥3 fatigue and neuropathy at some point during treatment. Conclusion Our comparison of complementary but distinct aspects of chemotherapy toxicity identified important longitudinal differences in fatigue and neuropathy by age and PS that are missed by the traditional maximum grade approach. Clinical trial identification number: NCT00003117 (CALGB 9730) Implications for Practice The traditional maximum grade approach ignores persistent low-grade adverse events (AEs) and changes over time. This toxicity over time analysis of fatigue and neuropathy during chemotherapy for advanced non-small cell lung cancer demonstrates how to use longitudinal methods to comprehensively characterize AEs over time by age and performance status (PS). We identified important longitudinal differences in fatigue and neuropathy that are missed by the maximum grade approach. This new information about how older adults and patients with PS 2 experience these toxicities longitudinally may be used clinically to improve discussions about treatment options and what to expect to inform shared decision making and symptom management.

Introduction Optimal treatment for older adults with stage III non-small cell lung cancer (NSCLC) remains unclear. Here we hypothesized that sequential chemoradiation therapy (sCRT) is better tolerated than concurrent (cCRT) but confers acceptable efficacy. We evaluated these strategies in older adults utilizing Alliance for Clinical Trials in Oncology data. Materials and methods Pooled analyses from 6 first-line stage III NSCLC CRT trials (Cancer and Leukemia Group B 8433, 8831, 9130, 30106, 30407, 39801) were used to compare toxicity and survival outcomes with cCRT versus sCRT in patients age ≥ 65 years. Grade 3–5 adverse events (AEs), progression-free and overall survival (PFS; OS) are reported with adjustment for covariates. Results Four hundred older adults, of whom 106 (26.5%) had received sCRT and 294 (73.5%) had received cCRT, comprised the cohorts. Virtually all had an Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1 (99%). More grade 3–5 AEs were observed at any time-point with cCRT than sCRT (94.2% versus 86.8%; 95% confidence interval for difference in proportions, 1.3%, 15.5%) and this finding remained after adjusting for length of study treatment (P = 0.018). Comparable PFS and OS were observed with sCRT versus cCRT (median: 8.0 versus 9.2 months; median: 11.9 versus 13.4 months, respectively) even after adjustment for age, sex, ECOG PS, body mass index, pretreatment weight loss, stage, and cisplatin-based therapy (P = 0.604 and P = 0.906, respectively). Discussion These data show that sCRT was associated with less toxicity than cCRT with no associated statistically significant decrease in efficacy outcomes and that sCRT merits further study in this population.

PURPOSE: While attentional function is an extremely important patient outcome for older adults, research on changes in function in this group is extremely limited. The purposes of this study were to: identify subgroups of older patients (i.e., latent growth classes) based on changes in their level of self-reported attentional function; determine which demographic and clinical characteristics were associated with subgroup membership; and determine if these subgroups differed on quality of life (QOL) outcomes. METHODS: Older oncology outpatients (n=365) who were assessed for changes in attention and working memory using the Attentional Function Index a total of six times over two cycles of chemotherapy (CTX). QOL was assessed using the Medical Outcomes Study-Short Form 12 and the QOL-Patient Version Scale. Latent profile analysis (LPA) was used to identify subgroups of older adults with distinct attentional function profiles. RESULTS: Three distinct attentional functional profiles were identified (i.e., low, moderate, and high attentional function). Compared to the high class, older adults in the low and moderate attentional function classes had lower functional status scores, a worse comorbidity profile and were more likely to be diagnosed with depression. In addition, QOL scores followed an expected pattern (low class < moderate class < high attentional function class). CONCLUSIONS: Three distinct attentional function profiles were identified among a relatively large sample of older adults undergoing CTX. The phenotypic characteristics associated with membership in the low and moderate latent classes can be used by clinicians to identify high risk patients.

Context Although physical function is an important patient outcome, little is known about changes in physical function in older adults receiving chemotherapy (CTX). Objectives Identify subgroups of older patients based on changes in their level of physical function; determine which demographic and clinical characteristics were associated with subgroup membership; and determine if these subgroups differed on quality-of-life (QOL) outcomes. Methods Latent profile analysis was used to identify groups of older oncology patients ( n = 363) with distinct physical function profiles. Patients were assessed six times over two cycles of CTX using the Physical Component Summary score from the Short Form 12. Differences, among the groups, in demographic and clinical characteristics and QOL outcomes were evaluated using parametric and nonparametric tests. Results Three groups of older oncology patients with distinct functional profiles were identified: Well Below (20.4%), Below (43.8%), and Above (35.8%) normative Physical Component Summary scores. Characteristics associated with membership in the Well Below class included the following: lower annual income, a higher level of comorbidity, being diagnosed with depression and back pain, and lack of regular exercise. Compared with the Above class, patients in the other two classes had significantly poorer QOL outcomes. Conclusion Almost 65% of older oncology patients reported significant decrements in physical function that persisted over two cycles of CTX. Clinicians can assess for those characteristics associated with poorer functional status to identify high-risk patients and initiate appropriate interventions.

15 Background: Discordance in prognostic understanding between caregivers of adults with cancer and the patient’s oncologist is common. However, the relationship between caregiver-oncologist discordance and caregiver bereavement outcomes is unknown. We evaluated the associations of caregiver-oncologist discordance in beliefs about the patient’s curability and life expectancy with caregiver-reported therapeutic alliance and anxiety. Methods: This is a secondary analysis of a multicenter study that assessed the effect of a communication intervention among patients with advanced cancer and their caregivers. Prior to intervention exposure, caregivers and oncologists were asked about their belief in the patient’s chances for cure and living ≥2 years: 100%, about 90%, about 75%, about 50/50, about 25%, about 10%, and 0%. Discordance was defined as a difference by 2 response levels on each prognostic understanding item. Outcomes at 7 months after patient death included caregiver-reported therapeutic alliance [modified 5-item Human Connection (THC) scale] and anxiety (Generalized Anxiety Disorder-7). We used multivariable linear regression models to assess the independent associations of discordance with therapeutic alliance and anxiety. Results: We included 97 caregivers (mean age 63, range 22-83). Approximately 40% of caregiver-oncologist dyads had discordant beliefs about curability (caregivers were more optimistic in 100% of dyads) and 63% had discordant beliefs about life expectancy (caregivers were more optimistic in 94% of dyads). On multivariate analysis, discordance in beliefs about prognostic estimates was associated with lower THC score (b = -6.94, SE 3.17, p = 0.03). Discordance in beliefs about curability was associated with lower anxiety levels (b = -1.79, SE 0.90, p = 0.05). Conclusions: Caregiver-oncologist discordance may decrease caregiver-reported therapeutic alliance and anxiety, both of which may shape how caregivers interact with the healthcare system. A better understanding the role of caregivers’ prognostic understanding will guide interventions to improve caregiver-oncologist therapeutic alliance and caregiver anxiety. Clinical trial information: NCT01485627.

Objectives Neutropenia is associated with the risk of life-threatening infections, chemotherapy dose reductions and delays that may compromise outcomes. This analysis was conducted to develop a prediction model for chemotherapy-induced severe neutropenia in lung cancer. Materials and Methods Individual patient data from existing cooperative group phase II/III trials of stages III/IV non-small cell lung cancer or extensive small-cell lung cancer were included. The data were split into training and testing sets. In order to enhance the prediction accuracy and the reliability of the prediction model, lasso method was used for both variable selection and regularization on the training set. The selected variables was fit to a logistic model to obtain regression coefficients. The performance of the final prediction model was evaluated by the area under the ROC curve in both training and testing sets. Results The dataset was randomly separated into training [7606 (67 %) patients] and testing [3746 (33 %) patients] sets. The final model included: age (>65 years), gender (male), weight (kg), BMI, insurance status (yes/unknown), stage (IIIB/IV/ESSCLC), number of metastatic sites (1, 2 or ≥3), individual drugs (gemcitabine, taxanes), number of chemotherapy agents (2 or ≥3), planned use of growth factors, associated radiation therapy, previous therapy (chemotherapy, radiation, surgery), duration of planned treatment, pleural effusion (yes/unknown), performance status (1, ≥2) and presence of symptoms (yes/unknown). Conclusions We have developed a relatively simple model with routinely available pre-treatment variables, to predict for neutropenia. This model should be independently validated prospectively.

Purpose Evaluate how subgroups of older adults with distinct attentional function profiles differ on the severity of nine common symptoms and determine demographic and clinical characteristics and symptom severity scores associated with membership in the low and moderate attentional function classes. Methods Three subgroups of older oncology outpatients were identified using latent profile analysis based on Attentional Function Index (AFI) scores. Symptoms were assessed prior to the second or third cycle of CTX. Logistic regressions evaluated for associations with attentional function class membership. Results For trait anxiety, state anxiety, depression, sleep disturbance, morning fatigue, and evening fatigue scores, differences among the latent classes followed the same pattern (low > moderate > high). For morning and evening energy, compared to high class, patients in low and moderate classes reported lower scores. For pain, compared to moderate class, patients in low class reported higher scores. In the logistic regression analysis, compared to high class, patients with lower income, higher comorbidity, higher CTX toxicity score, and higher levels of state anxiety, depression, and sleep disturbance were more likely to be in low AFI class. Compared to high class, patients with higher comorbidity and trait anxiety and lower morning energy were more likely to be in moderate AFI class. Conclusions Consistent with the hypothesis that an increased risk for persistent cognitive decline is likely related to a variety of physical and psychological factors, for six of the nine symptoms, a “dose response” effect was observed with higher symptom severity scores associated with a progressive decline in attentional function.

Chemotherapy-related cognitive impairment (CRCI) can occur during or after chemotherapy and represents a concern for many patients with cancer. Among older patients with cancer, in whom there is little clinical trial evidence examining side effects like CRCI, many unanswered questions remain regarding risk for and resulting adverse outcomes from CRCI. Given the rising incidence of cancer with age, CRCI is of particular concern for older patients with cancer who receive treatment. Therefore, research related to CRCI in older patients with cancers is a high priority. In this manuscript, we discuss current gaps in research highlighting the lack of clinical studies of CRCI in older adults, the complex mechanisms of CRCI, and the challenges in measuring cognitive impairment in older patients with cancer. Although we focus on CRCI, we also discuss cognitive impairment related to cancer itself and other treatment modalities. We highlight several research priorities to improve the study of CRCI in older patients with cancer.

Purpose Older adults receiving cancer chemotherapy are at increased risk for decrements in physical (PF) and cognitive (CF) function. Objectives Study identified subgroups of patients with distinct PF and CF profiles; risk factors associated with subgroup membership; and impact of subgroup membership on quality of life (QOL). Methods In 366 older oncology patients, PF and CF were assessed using the Physical Component Summary (PCS) of the SF-12 and Attentional Function Index, respectively. Latent profile analysis was used to identify subgroups of older patients with distinct PF/CF profiles. Results Three distinct PF/CF profiles were identified (i.e., Very Low PF + Moderate CF (15.6%); Low PF + Low CF (39.3%), Normal PF + Normal CF (45.1%)). Compared to the both Normal class, patients in the other two classes had a lower functional status, a worse comorbidity profile, and were less likely to exercise on a regular basis. Compared to the Both Normal class, patients in the Both Low class were less likely to be married/partnered, more likely to live alone, less likely to be employed, and more likely to report depression and back pain. Compared to the other two classes, patients in the Both Low class had a lower annual household income and were receiving chemotherapy with a worse toxicity profile. Conclusion First study to use a person-centered analytic approach to identify subgroups of older adults with distinct PF/CF profiles. Fifty-five percent of the older adults had statistically significant and clinically meaningful decrements in both PF AND CF that had negative effects on all aspects of QOL.

Key Points Question Is exposure to the National Comprehensive Cancer Center guidelines associated with decreased decisional conflict and increased rates of guideline-concordant care in patients with non–small cell lung cancer? Findings In this nonrandomized clinical trial, exposure to the National Comprehensive Cancer Center guidelines in 76 patients with non–small cell lung cancer was associated with increased smoking cessation counseling and decreased use of adjuvant chemotherapy after resection of early-stage disease. Use of the tool during consultation was also associated with decreased decisional conflict and greater satisfaction with their decision by the patients. Meaning The findings of this study suggest that use of cancer treatment guidelines is not in conflict with shared decision-making; increasing patients’ access to guidelines appears to improve the quality of oncologic care., Importance The association of guideline-based decision support with the quality of care in patients with non–small cell lung cancer (NSCLC) is not known. Objective To evaluate the association of exposure to the National Comprehensive Cancer Center (NCCN) guidelines with guideline-concordant care and patients’ decisional conflict. Design, Setting, and Participants A nonrandomized clinical trial, conducted at a tertiary care academic institution, enrolled patients from February 23, 2015, to September 28, 2017. Data analysis was conducted from July 19, 2019, to April 22, 2020. A cohort of 76 patients with NSCLC seen at diagnosis or disease progression and a retrospective cohort of 157 patients treated before the trial were included. Adherence to 6 NCCN recommendations were evaluated: (1) smoking cessation counseling, (2) adjuvant chemotherapy for patients with stage IB to IIB NSCLC after surgery, (3) pathologic mediastinal staging in patients with stage III NSCLC before surgery, (4) pathologic mediastinal staging in patients with stage III NSCLC before nonsurgical treatment, (5) definitive chemoradiotherapy for patients with stage III NSCLC not having surgery, and (6) molecular testing for epidermal growth factor receptor and anaplastic lymphoma kinase alterations for patients with stage IV NSCLC. Subgroup analysis was conducted to compare the rates of guideline concordance between the prospective and retrospective cohorts. Secondary end points included decisional conflict and satisfaction. Interventions An online tool customizing the NCCN guidelines to patients’ clinical and pathologic features was used during consultation, facilitated by a trained coordinator. Main Outcomes and Measures Concordance of practice with 6 NCCN treatment recommendations on NSCLC and patients’ decisional conflict. Results Of the 76 patients with NSCLC, 44 were men (57.9%), median age at diagnosis was 68 years (interquartile range [IQR], 41-87 years), and 59 patients (77.6%) had adenocarcinoma. In the retrospective cohort, 91 of 157 patients (58.0%) were men, median age at diagnosis was 66 years (IQR, 61-65 years), and 105 patients (66.9%) had adenocarcinoma. After the intervention, patients received more smoking cessation counseling (4 of 5 [80.0%] vs 1 of 24 [4.2%], P, This nonrandomized clinical trial examines the inclusion of National Comprehensive Cancer Network (NCCN) guidelines in a tool used by patients with non–small cell lung cancer to facilitate decision-making.

PURPOSE: While older adults with cancer are more likely to develop chemotherapy-induced peripheral neuropathy (CIPN), the study aimed to determine if patient-reported and objective measures of CIPN differ by age among cancer survivors. METHODS: Cancer survivors with persistent CIPN after completion of platinum and/or taxane chemotherapy completed CIPN questionnaires (severity, interference with activities, sensory and motor symptoms) and objective testing (light touch, vibration, pain, cold sensation). CIPN measures were compared by age group (

Purpose: Accurate comorbidity measurement is critical for cancer research. We evaluated comorbidity assessment in the National Cancer Database (NCDB), which uses a code-based Charlson-Deyo Comorbidity Index (CCI), and compared its prognostic performance with a chart-based CCI and individual comorbidities in a national sample of patients with breast, colorectal, or lung cancer. Patients and Methods: Through an NCDB Special Study, cancer registrars re-abstracted perioperative comorbidities for 11,243 patients with stage II to III breast cancer, 10,880 with stage I to III colorectal cancer, and 9,640 with stage I to III lung cancer treated with definitive surgical resection in 2006-2007. For each cancer type, we compared the prognostic performance of the NCDB code-based CCI (categorical: 0 or missing data, 1, 2+), Special Study chart-based CCI (continuous), and 18 individual comorbidities in three separate Cox proportional hazards models for postoperative 5-year overall survival. Results: Comorbidity was highest among patients with lung cancer (13.2% NCDB CCI 2+) and lowest among patients with breast cancer (2.8% NCDB CCI 2+). Agreement between the NCDB and Special Study CCI was highest for breast cancer (rank correlation, 0.50) and lowest for lung cancer (rank correlation, 0.40). The NCDB CCI underestimated comorbidity for 19.1%, 29.3%, and 36.2% of patients with breast, colorectal, and lung cancer, respectively. Within each cancer type, the prognostic performance of the NCDB CCI, Special Study CCI, and individual comorbidities to predict postoperative 5-year overall survival was similar. Conclusion: The NCDB underestimated comorbidity in patients with surgically resected breast, colorectal, or lung cancer, partly because the NCDB codes missing data as CCI 0. However, despite underestimation of comorbidity, the NCDB CCI was similar to the more complete measures of comorbidity in the Special Study in predicting overall survival.

To evaluate whether an association exists between the intensity of surveillance following surgical resection for non-small cell lung cancer (NSCLC) and survival.Surveillance guidelines following surgical resection of NSCLC vary widely and are based on expert opinion and limited evidence.A Special Study of the National Cancer Database randomly selected stage I to III NSCLC patients for data reabstraction. For patients diagnosed between 2006 and 2007 and followed for 5 years through 2012, registrars documented all postsurgical imaging with indication (routine surveillance, new symptoms), recurrence, new primary cancers, and survival, with 5-year follow-up. Patients were placed into surveillance groups according to existing guidelines (3-month, 6-month, annual). Overall survival and survival after recurrence were analyzed using Cox Proportional Hazards Models.A total of 4463 patients were surveilled with computed tomography scans; these patients were grouped based on time from surgery to first surveillance. Groups were similar with respect to age, sex, comorbidities, surgical procedure, and histology. Higher-stage patients received more surveillance. More frequent surveillance was not associated with longer risk-adjusted overall survival [hazard ratio for 6-month: 1.16 (0.99, 1.36) and annual: 1.06 (0.86-1.31) vs 3-month; P value 0.14]. More frequent imaging was also not associated with postrecurrence survival [hazard ratio: 1.02/month since imaging (0.99-1.04); P value 0.43].These nationally representative data provide evidence that more frequent postsurgical surveillance is not associated with improved survival. As the number of lung cancer survivors increases over the next decade, surveillance is an increasingly important major health care concern and expenditure.

ContextAn important question in symptom clusters research is whether the number and types of symptom clusters vary based on the specific dimension of the symptom experience used to create the clusters.ObjectivesGiven that lung cancer patients undergoing chemotherapy (CTX) report an average of 14 co-occurring symptoms and studies of symptom clusters in these patients are limited, the purpose of this study, in lung cancer patients undergoing CTX (n=145), was to identify whether the number and types of symptom clusters differed based on whether symptom occurrence rates or symptom severity ratings were used to create the clusters.MethodsA modified version of the Memorial Symptom Assessment Scale was used to assess for the occurrence and severity of 38 symptoms, one week after the administration of CTX. Exploratory factor analysis was used to extract the symptom clusters.ResultsBoth the number and types of symptom clusters were relatively similar using symptom occurrence rates or symptom severity ratings. Five symptom clusters were identified using both symptom occurrence rates and severity ratings (i.e., sickness behavior, lung cancer specific, psychological, nutritional, and epithelial). Across these two dimensions, the specific symptoms within each of the symptom clusters were relatively similar.ConclusionsIdentification of symptom clusters in patients with lung cancer may assist with the development of more targeted symptom management interventions. Future studies are warranted to determine if symptom clusters change over a cycle of CTX in patients with lung cancer.

PurposeFew studies have examined interindividual variability in the symptom experience of lung cancer patients. We aimed to identify the most prevalent, severe, and distressing symptoms, and risk factors associated with increased symptom burden.MethodsLung cancer patients (n=145) reported occurrence, severity, and distress for 38 symptoms on the Memorial Symptom Assessment Scale 1week after chemotherapy. Using multidimensional subscales, risk factors for higher global distress, physical, and psychological symptoms were evaluated using simultaneous linear regression.ResultsMean age was 64.0years and 56.6% were female. Mean Karnofsky Performance Status score was 79.1 (SD 14.6) and mean Self-Administered Comorbidity Questionnaire score was 7.3 (SD 3.9). The most distressing and prevalent symptom was fatigue. Problems with sexual interest/activity had the highest mean severity rating. Patients with lower functional status (p=0.001) and higher comorbidity (p=0.02) reported higher global distress. Similarly, lower functional status (p=0.003) and higher comorbidity (p=0.04) were associated with a higher physical symptom burden along with lower body mass index (p=0.02). Higher psychology symptom burden was associated with lower functional status (p=0.01), younger age (p=0.02), non-metastatic disease (p=0.03), higher number of prior treatments (p=0.04), and income (p=0.03).ConclusionsFatigue was the most distressing and prevalent symptom among lung cancer patients receiving chemotherapy. Lower functional status was associated with a higher burden of global distress, physical, and psychological symptoms. Younger age and non-metastatic disease were additional risk factors for increased psychological symptoms. Together, these risk factors can help clinicians identify lung cancer patients at increased need for aggressive symptom management.

ObjectiveOlder patients with non-small cell lung cancer (NSCLC) are less likely to receive guideline-recommended treatment at diagnosis, independent of comorbidity. However, national data on treatment of postoperative recurrence are limited. We evaluated the associations between age, comorbidity, and other patient factors and treatment of postoperative NSCLC recurrence in a national cohort.Materials and methodsWe randomly selected 9001 patients with surgically resected stage I-III NSCLC in 2006-2007 from the National Cancer Data Base. Patients were followed for 5 years or until first NSCLC recurrence, new primary cancer, or death, whichever came first. Perioperative comorbidities, first recurrence, treatment of recurrence, and survival were abstracted from medical records and merged with existing registry data. Factors associated with active treatment (chemotherapy, radiation, and/or surgery) versus supportive care only were analyzed using multivariable logistic regression.ResultsMedian age at initial diagnosis was 67; 69.7% had >1 comorbidity. At 5-year follow-up, 12.3% developed locoregional and 21.5% developed distant recurrence. Among patients with locoregional recurrence, 79.5% received active treatment. Older patients (OR 0.49 for age >75 compared with 75 compared with

ImportanceDespite guidelines recommending against prostate-specific antigen (PSA) screening in elderly men with limited life expectancy, PSA screening remains common.ObjectiveTo identify clinician characteristics associated with PSA screening rates in older veterans stratified by life expectancy.Design, setting, and participantsCross-sectional study of 826 286 veterans 65 years or older eligible for PSA screening who had VA laboratory tests performed in 2011 in the VA health care system.Main outcomes and measuresThe primary outcome was the percentage of men with a screening PSA test in 2011. Limited life expectancy was defined as age of at least 85 years with Charlson comorbidity score of 1 or greater or age of at least 65 years with Charlson comorbidity score of 4 or greater. Primary predictors were clinician characteristics including degree-training level, specialty, age, and sex. We performed log-linear Poisson regression models for the association between each clinician characteristic and PSA screening stratified by patient life expectancy and adjusted for patient demographics and clinician clustering.ResultsIn 2011, 466 017 (56%) of older veterans received PSA screening, including 39% of the 203 717 men with limited life expectancy. After adjusting for patient demographics, higher PSA screening rates in patients with limited life expectancy was associated with having a clinician who was an older man and was no longer in training. The PSA screening rates ranged from 27% for men with a physician trainee to 42% for men with an attending physician (P

Purpose Because comorbidity affects cancer treatment outcomes, guidelines recommend considering comorbidity when making treatment decisions in older patients with lung cancer. Yet, it is unclear whether treatment is targeted to healthier older adults who might reasonably benefit. Patients and Methods Receipt of first-line guideline-recommended treatment was assessed for 20,511 veterans age ≥ 65 years with non–small-cell lung cancer (NSCLC) in the Veterans Affairs (VA) Central Cancer Registry from 2003 to 2008. Patients were stratified by age (65 to 74, 75 to 84, ≥ 85 years), Charlson comorbidity index score (0, 1 to 3, ≥ 4), and American Joint Committee on Cancer stage (I to II, IIIA to IIIB, IIIB with malignant effusion to IV). Comorbidity and patient characteristics were obtained from VA claims and registry data. Multivariate analysis identified predictors of receipt of guideline-recommended treatment. Results In all, 51% of patients with local, 35% with regional, and 27% with metastatic disease received guideline-recommended treatment. Treatment rates decreased more with advancing age than with worsening comorbidity for all stages, such that older patients with no comorbidity had lower rates than younger patients with severe comorbidity. For example, 50% of patients with local disease age 75 to 84 years with no comorbidity received surgery compared with 57% of patients age 65 to 74 years with severe comorbidity (P < .001). In multivariate analysis, age and histology remained strong negative predictors of treatment for all stages, whereas comorbidity and nonclinical factors had a minor effect. Conclusion Advancing age is a much stronger negative predictor of treatment receipt among older veterans with NSCLC than comorbidity. Individualized decisions that go beyond age and include comorbidity are needed to better target NSCLC treatments to older patients who may reasonably benefit.

Context Studies on physical function trajectories in older adults during chemotherapy remain limited. Objectives The objective of this study was to determine demographic, clinical, and symptom characteristics associated with initial levels as well as trajectories of physical function over two cycles of chemotherapy in adults aged ≥65 years with breast, gastrointestinal, gynecological, or lung cancer. Methods Older adults with cancer (n = 363) who had received chemotherapy within the preceding four weeks were assessed six times over two cycles of chemotherapy using the Short Form-12 Physical Component Summary (PCS) score. Hierarchical linear modeling was used to evaluate for interindividual variability in initial levels and trajectories of PCS scores. Results Mean age was 71.4 years (SD 5.5). Mean PCS score at enrollment was 40.5 (SD .45). On average, PCS scores decreased slightly (i.e., 0.21 points) at each subsequent assessment. Lower PCS scores at enrollment were associated with older age, greater comorbidity, being unemployed, lack of regular exercise, higher morning fatigue, lower evening energy, occurrence of pain, lower trait anxiety, and lower attentional function. Only higher morning fatigue and lower enrollment PCS scores were associated with decrements in physical function over time. Conclusion While several symptoms were associated with decrements in PCS scores at enrollment in older adults with cancer receiving chemotherapy, morning fatigue was the only symptom associated with decreases in physical function over time. Regular assessments of symptoms and implementation of evidence-based interventions should be considered to maintain physical function in older adults during chemotherapy.

This study examined perceived social support among children of parents diagnosed with cancer. Twenty-nine participants, ages 18-38, who had been children when one of their parents was diagnosed with cancer provided demographic information and participated in an interview about the impact of their parent's illness on their lives. Five common themes characterized participants' perceived social support received during their parent's illness: (a) listening and understanding; (b) encouragement and reassurance; (c) tangible assistance; (d) communication about cancer and treatment; and (e) engaging in normal life experiences. Depending on the circumstances, however, a given type of social support was perceived to be helpful to some, while perceived by others as ineffective or detrimental. Differences in respondents' perceptions of the effects of specific forms of received social support speak to the need for individualized support for children of cancer patients based upon each child's specific needs and circumstances.

Cancer and neurocognitive disorders, such as dementia and delirium, are common and serious diseases in the elderly that are accompanied by high degree of morbidity and mortality. Furthermore, evidence supports the under-diagnosis of both dementia and delirium in older adults. Complex questions exist regarding the interaction of dementia and delirium with cancer, beginning with guidelines on how best measure disease severity, the optimal screening test for either disorder, the appropriate level of intervention in the setting of abnormal findings, and strategies aimed at preventing the development or progression of either process. Ethical concerns emerge in the research setting, pertaining to the detection of cognitive dysfunction in participants, validity of consent, disclosure of abnormal results if screening is pursued, and recommended level of intervention by investigators. Furthermore, understanding the ways in which comorbid cognitive dysfunction and cancer impact both cancer and non-cancer-related outcomes is essential in guiding treatment decisions. In the following article, we will discuss what is presently known of the interactions of pre-existing cognitive impairment and delirium with cancer. We will also discuss identified deficits in our knowledge base, and propose ways in which innovative research may address these gaps.

This study examined predictors of posttraumatic stress disorder (PTSD) symptoms in adults who, as children, had a parent diagnosed with cancer. Possible predictors of adulthood PTSD examined were peritraumatic dissociation, satisfaction with social support, coping through denial, behavioral disengagement and self-distraction, and whether or not the parent died. Thirty research participants (20 women and 10 men, ages 18–38) were recruited who were 8–17-years old at the time of a parent's cancer diagnosis. Each participant completed measures of their current PTSD symptoms in response to their parent's cancer, peritraumatic dissociative experiences, demographic characteristics, and satisfaction with social support and use of coping strategies at the time of their parent's cancer diagnosis. Seventeen percent met screening criteria for likely PTSD. As hypothesized, PTSD symptoms were strongly and positively correlated with peritraumatic dissociation. Furthermore, PTSD symptoms were greater among females and were related to greater use of denial and behavioral disengagement and to less satisfaction with social support. These results suggest that health care providers need to recognize symptoms of peritraumatic dissociation in the children of parents who are diagnosed with cancer so that steps can be taken to minimize the children's development of PTSD that may extend into their adult lives. Copyright © 2006 John Wiley & Sons, Ltd.

INTRODUCTION: Lung cancer incidence is associated with markers of lower socioeconomic status (SES) in whites, blacks, and Asians but with markers of higher SES in Hispanics. The magnitude and etiology of this positive gradient in Hispanics remain undefined. We examined non-small-cell lung cancer (NSCLC) incidence and ever-smoking rates among California Hispanics according to measures of SES. METHODS: We computed neighborhood (n)SES-specific incidence rates by sex and race or ethnicity for 74,179 NSCLC cases in the California Cancer Registry, 1998-2002. Associations between nSES and NSCLC incidence were examined, using incidence rate ratios and linear trend tests, and stratified by age, stage, and histology. Ever-smoking rates among Hispanics were obtained from California Health Interview Survey 2001 data, and odds ratios for ever-smoking were calculated for measures of SES and acculturation. RESULTS: Compared with the lowest nSES quintile, the NSCLC incidence in the highest quintile was 1.86 and 1.18 times higher for Hispanic women and men, respectively. The positive nSES gradients remained significant for all ages, stages, and nonsquamous histologies in women, and only for older age, local or regional stages, and adenocarcinoma histology in men. Ever-smoking rates were associated with English-speaking households and U.S.-born status for Hispanic women and low education and U.S.-born status for Hispanic men. CONCLUSIONS: For California Hispanics, higher nSES was strongly associated with increased NSCLC incidence in women, but weakly associated in men, and ever-smoking rates were strongly correlated with increased acculturation. This finding may portend an increasing burden of NSCLC in Hispanic women, given future trends in acculturation and SES. Copyright © 2013 by the International Association for the Study of Lung Cancer.

A series of compounds were designed and synthesized as antagonists of cIAP1/2, ML-IAP, and XIAP based on the N-terminus, AVPI, of mature Smac. Compound 1 (GDC-0152) has the best profile of these compounds; it binds to the XIAP BIR3 domain, the BIR domain of ML-IAP, and the BIR3 domains of cIAP1 and cIAP2 with K(i) values of 28, 14, 17, and 43 nM, respectively. These compounds promote degradation of cIAP1, induce activation of caspase-3/7, and lead to decreased viability of breast cancer cells without affecting normal mammary epithelial cells. Compound 1 inhibits tumor growth when dosed orally in the MDA-MB-231 breast cancer xenograft model. Compound 1 was advanced to human clinical trials, and it exhibited linear pharmacokinetics over the dose range (0.049 to 1.48 mg/kg) tested. Mean plasma clearance in humans was 9 ± 3 mL/min/kg, and the volume of distribution was 0.6 ± 0.2 L/kg.

This study examined the long-term impact of parental cancer during childhood. Nineteen female and 8 male adults who had a parent with terminal or nonterminal cancer during childhood participated in face-to-face interviews during which they discussed how their parent's cancer affected their lives. Their interview responses were transcribed and analyzed using a constant comparative method of analysis. Posttraumatic growth experiences were reported by 44% of participants, and 59% reported adverse consequences. Future research should examine ways to identify factors that can help affected children experience posttraumatic growth while minimizing the adverse consequences of having a parent with cancer.

A 64-year-old Mexican fisherman with a history of syphilis is diagnosed with panuveitis of the right eye after presenting with unilateral blurry vision, redness, and pain. A PPD was 35X30mm, and chest X-ray suggested tuberculosis. The patient’s pain and vision improved with 4-drug anti-tuberculous therapy, topical steroids, and cycloplegic eye drops.